The Experts below are selected from a list of 13053 Experts worldwide ranked by ideXlab platform
Roderick H.j. Houwen - One of the best experts on this subject based on the ideXlab platform.
-
Familial Cholestasis: Progressive familial Intrahepatic Cholestasis, benign recurrent Intrahepatic Cholestasis and Intrahepatic Cholestasis of pregnancy
Best Practice & Research in Clinical Gastroenterology, 2010Co-Authors: Wendy L. Van Der Woerd, Janneke M Stapelbroek, Stan F J Van De Graaf, Leo W. J. Klomp, Roderick H.j. HouwenAbstract:Progressive familial Intrahepatic Cholestasis (PFIC) type 1, 2 and 3 are due to mutations in ATP8B1, ABCB11 and ABCB4, respectively. Each of these genes encodes a hepatocanalicular transporter, which is essential for the proper formation of bile. Mutations in ABCB4 can result in progressive cholestatic disease, while mutations in ATP8B1 and ABCB11 can result both in episodic Cholestasis, referred to as benign recurrent Intrahepatic Cholestasis (BRIC) type 1 and 2, as well as in progressive cholestatic disease. This suggests a clinical continuum and these diseases are therefore preferably referred to as ATP8B1 deficiency and ABCB11 deficiency. Similarly PFIC type 3 is designated as ABCB4 deficiency. Heterozygous mutations in each of these transporters can also be associated with Intrahepatic Cholestasis of pregnancy. This review summarizes the pathophysiology, clinical features and current as well as future therapeutic options for progressive familial- and benign recurrent Intrahepatic Cholestasis as well as Intrahepatic Cholestasis of pregnancy.
-
benign recurrent Intrahepatic Cholestasis progressing to progressive familial Intrahepatic Cholestasis low ggt Cholestasis is a clinical continuum
Journal of Hepatology, 2002Co-Authors: Nancy A M Van Ooteghem, Leo W. J. Klomp, Gerard P Van Bergehenegouwen, Roderick H.j. HouwenAbstract:Benign recurrent Intrahepatic Cholestasis (BRIC) is an autosomal recessive liver disease, characterised by intermittent attacks of Cholestasis, which can start at any age and last for several weeks to months. Characteristically serum GGT activity is low and normal liver structure is preserved. Progressive familial Intrahepatic Cholestasis (PFIC) is another liver disease, characterised by severe Cholestasis, starting almost invariably before 6 months of age. All patients progress to cirrhosis, liver failure and death, unless a liver transplantation is performed. We now identified four patients who presented in childhood with recurrent attacks of Cholestasis, while in the course of the disease the Cholestasis gradually became permanent. Although liver biopsies performed in the early stages of the disease showed normal liver architecture, late stage biopsies revealed evident fibrosis with porto-portal septa formation. In conclusion, the disease of these patients started with the clinical and histopathological characteristics of BRIC but progressed to PFIC.
A S Knisely - One of the best experts on this subject based on the ideXlab platform.
-
polymorphisms in abcb11 and atp8b1 associated with development of severe Intrahepatic Cholestasis in hodgkin s lymphoma
Journal of clinical and experimental hepatology, 2013Co-Authors: Laura Blackmore Blackmore, Jane Hartley, K Mckay, Paul Gissen, A S Knisely, Robert Marcus, Debbie L ShawcrossAbstract:We report a young man presenting with jaundice and severe debilitating Intrahepatic Cholestasis 7 months before the diagnosis of Hodgkin's lymphoma. Serum gamma-glutamyl transferase (GGT) activity was not raised. Liver biopsy demonstrated deficiency of canalicular GGT and bile salt export pump expression, which suggested “benign” recurrent Intrahepatic Cholestasis. Direct sequencing of genomic DNA was therefore undertaken to look for mutations in ATP8B1 and ABCB11. Cholestasis and pruritus are well recognized presenting features of Hodgkin's lymphoma. However, striking in this case is that the Intrahepatic Cholestasis presented and resolved 7 months before the diagnosis. Furthermore, 4 polymorphisms were identified in ATP8B1 in this patient—c.696T > C (rs319438), c.811A > C (rs319438), c.2855G > A (rs1296811) and c.3454G > A (rs222581)—and two polymorphisms in ABCB11—c.1331T > C (rs2287622) and c.3084A > G (rs497692); 2 of which have been associated with Intrahepatic Cholestasis of pregnancy. We therefore postulate that these polymorphisms predisposed this patient to the development of Intrahepatic Cholestasis within the abnormal pro-inflammatory cytokine milieu typical for Hodgkin's lymphoma. This case shows for the first time that some polymorphisms in ABCB11 and ATP8B1 may predispose to the development of Intrahepatic Cholestasis in Hodgkin's lymphoma. It also demonstrates the importance of close clinical surveillance for the development of Hodgkin's lymphoma in patients presenting with unexplained Intrahepatic Cholestasis.
-
Progressive Familial Intrahepatic Cholestasis in Children
Concise Pediatric and Adolescent Hepatology, 2012Co-Authors: A S KniselyAbstract:Progressive familial Intrahepatic Cholestasis is a group of inherited disorders that have been identified in the last two decades. Infants presenting with mild to severe jaundice, low GGT (FIC1, FIC2)
-
progressive familial Intrahepatic Cholestasis type 1 is associated with decreased farnesoid x receptor activity
Gastroenterology, 2004Co-Authors: Frank Chen, A S Knisely, Laura N. Bull, Meenakshisundaram Ananthanarayanan, Sukru Emre, Ezequiel Neimark, Sandra Strautnieks, Richard Thompson, Margret S Magid, Ronald E GordonAbstract:Abstract Background & Aims: The mechanisms by which mutations in the familial Intrahepatic Cholestasis-1 gene cause Byler's disease (progressive familial Intrahepatic Cholestasis type 1) are unknown. Methods: Interactions among the apical sodium-dependent bile acid transporter, the farnesoid X receptor (FXR), and familial Intrahepatic Cholestasis-1 were studied in the ileum of children with progressive familial Intrahepatic Cholestasis type 1 and in Caco-2 cells. Results: Increased ileal apical sodium-dependent bile acid transporter messenger RNA (mRNA) expression was detected in 3 patients with progressive familial Intrahepatic Cholestasis type 1. Paradoxically, ileal lipid-binding protein mRNA expression was repressed, suggesting a central defect in bile acid response. Ileal FXR and short heterodimer partner mRNA levels were reduced in the same 3 patients. In Caco-2 cells, antisense-mediated knock-down of endogenous familial Intrahepatic Cholestasis-1 led to up-regulation of apical sodium-dependent bile acid transporter and down-regulation of FXR, ileal lipid-binding protein, and short heterodimer partner mRNA. In familial Intrahepatic Cholestasis-1-negative Caco-2 cells, the activity of the human apical sodium-dependent bile acid transporter promoter was enhanced, whereas the human FXR and bile salt excretory pump promoters' activities were reduced. Overexpression of short heterodimer partner but not of the FXR abrogated the effect of familial Intrahepatic Cholestasis-1 antisense oligonucleotides. FXR cis -element binding and FXR protein were reduced primarily in nuclear but not cytoplasmic extracts from familial Intrahepatic Cholestasis-1-negative Caco-2 cells. Conclusions: Loss of familial Intrahepatic Cholestasis-1 leads to diminished nuclear translocation of the FXR, with the subsequent potential for pathologic alterations in intestinal and hepatic bile acid transporter expression. Marked hypercholanemia and Cholestasis are predicted to develop, presumably because of both enhanced ileal uptake of bile salts via up-regulation of the apical sodium-dependent bile acid transporter and diminished canalicular secretion of bile salts secondary to down-regulation of the bile salt excretory pump.
Leo W. J. Klomp - One of the best experts on this subject based on the ideXlab platform.
-
Familial Cholestasis: Progressive familial Intrahepatic Cholestasis, benign recurrent Intrahepatic Cholestasis and Intrahepatic Cholestasis of pregnancy
Best Practice & Research in Clinical Gastroenterology, 2010Co-Authors: Wendy L. Van Der Woerd, Janneke M Stapelbroek, Stan F J Van De Graaf, Leo W. J. Klomp, Roderick H.j. HouwenAbstract:Progressive familial Intrahepatic Cholestasis (PFIC) type 1, 2 and 3 are due to mutations in ATP8B1, ABCB11 and ABCB4, respectively. Each of these genes encodes a hepatocanalicular transporter, which is essential for the proper formation of bile. Mutations in ABCB4 can result in progressive cholestatic disease, while mutations in ATP8B1 and ABCB11 can result both in episodic Cholestasis, referred to as benign recurrent Intrahepatic Cholestasis (BRIC) type 1 and 2, as well as in progressive cholestatic disease. This suggests a clinical continuum and these diseases are therefore preferably referred to as ATP8B1 deficiency and ABCB11 deficiency. Similarly PFIC type 3 is designated as ABCB4 deficiency. Heterozygous mutations in each of these transporters can also be associated with Intrahepatic Cholestasis of pregnancy. This review summarizes the pathophysiology, clinical features and current as well as future therapeutic options for progressive familial- and benign recurrent Intrahepatic Cholestasis as well as Intrahepatic Cholestasis of pregnancy.
-
benign recurrent Intrahepatic Cholestasis progressing to progressive familial Intrahepatic Cholestasis low ggt Cholestasis is a clinical continuum
Journal of Hepatology, 2002Co-Authors: Nancy A M Van Ooteghem, Leo W. J. Klomp, Gerard P Van Bergehenegouwen, Roderick H.j. HouwenAbstract:Benign recurrent Intrahepatic Cholestasis (BRIC) is an autosomal recessive liver disease, characterised by intermittent attacks of Cholestasis, which can start at any age and last for several weeks to months. Characteristically serum GGT activity is low and normal liver structure is preserved. Progressive familial Intrahepatic Cholestasis (PFIC) is another liver disease, characterised by severe Cholestasis, starting almost invariably before 6 months of age. All patients progress to cirrhosis, liver failure and death, unless a liver transplantation is performed. We now identified four patients who presented in childhood with recurrent attacks of Cholestasis, while in the course of the disease the Cholestasis gradually became permanent. Although liver biopsies performed in the early stages of the disease showed normal liver architecture, late stage biopsies revealed evident fibrosis with porto-portal septa formation. In conclusion, the disease of these patients started with the clinical and histopathological characteristics of BRIC but progressed to PFIC.
Alfredo M Germain - One of the best experts on this subject based on the ideXlab platform.
-
Intrahepatic Cholestasis of Pregnancy: An Intriguing Pregnancy-Specific Disorder
The Journal of the Society for Gynecologic Investigation: JSGI, 2002Co-Authors: Alfredo M Germain, Jorge A. Carvajal, Juan Carlos Glasinovic, Kato C. Sumie, Catherine WilliamsonAbstract:Objective To review animal and human data available regarding the etiology, maternal and fetal impact, and treatment of Intrahepatic Cholestasis of pregnancy (ICP). Methods Pertinent studies on human and animal models of ICP were selected through a MEDLINE database search, focusing on etiology and clinical impact of the disease. Analytic and descriptive studies were included, and the data were analyzed looking for crude numbers. Results Intrahepatic Cholestasis of pregnancy is a pregnancy-specific disorder. Its prevalence is higher in Chile and Sweden compared with any other population. Its etiology is largely unknown, although endocrine, genetic, and environmental factors have been postulated as responsible for the appearance of the disease. Maternal effects of ICP are mild; however, there is a clear association between ICP and poor perinatal outcome, including a higher frequency of fetal distress, preterm labor and delivery, and unexplained fetal death. The treatment is mainly symptomatic. Recent data suggest that oral use of ursodeoxycholic acid improves maternal condition and might prevent the fetal complications of ICP. Conclusions Intrahepatic Cholestasis of pregnancy should be considered a high-risk condition, and careful fetal assessment and appropriate medical intervention might improve perinatal outcome.
-
Intrahepatic Cholestasis of pregnancy a retrospective case control study of perinatal outcome
American Journal of Obstetrics and Gynecology, 1994Co-Authors: Alonso J Rioseco, Milenko Ivankovic, Alejandro Manzur, Fuad Hamed, Sumie R Kato, Julian T Parer, Alfredo M GermainAbstract:Abstract OBJECTIVES: Intrahepatic Cholestasis of pregnancy has been related to a high frequency of abnormal intrapartum fetal heart rate, amniotic fluid meconium, prematurity, and perinatal mortality. To determine whether these adverse perinatal outcomes could be improved with active intervention, we evaluated our results. STUDY DESIGN: We report a retrospective case-control study of 320 consecutive patients with Intrahepatic Cholestasis of pregnancy management with antepartum testing and active intervention over a 2-year period. RESULTS: Our results indicate a higher incidence of meconium staining in amniotic fluid at delivery (25% vs 16%, p p CONCLUSION: Antenatal testing and timed intervention of patients with Intrahepatic Cholestasis of pregnancy is associated with a reduction of the previously reported adverse perinatal outcomes. (AM J OBSTET GYNECOL 1994;170:890-5.)
Nancy A M Van Ooteghem - One of the best experts on this subject based on the ideXlab platform.
-
benign recurrent Intrahepatic Cholestasis progressing to progressive familial Intrahepatic Cholestasis low ggt Cholestasis is a clinical continuum
Journal of Hepatology, 2002Co-Authors: Nancy A M Van Ooteghem, Leo W. J. Klomp, Gerard P Van Bergehenegouwen, Roderick H.j. HouwenAbstract:Benign recurrent Intrahepatic Cholestasis (BRIC) is an autosomal recessive liver disease, characterised by intermittent attacks of Cholestasis, which can start at any age and last for several weeks to months. Characteristically serum GGT activity is low and normal liver structure is preserved. Progressive familial Intrahepatic Cholestasis (PFIC) is another liver disease, characterised by severe Cholestasis, starting almost invariably before 6 months of age. All patients progress to cirrhosis, liver failure and death, unless a liver transplantation is performed. We now identified four patients who presented in childhood with recurrent attacks of Cholestasis, while in the course of the disease the Cholestasis gradually became permanent. Although liver biopsies performed in the early stages of the disease showed normal liver architecture, late stage biopsies revealed evident fibrosis with porto-portal septa formation. In conclusion, the disease of these patients started with the clinical and histopathological characteristics of BRIC but progressed to PFIC.